The present invention relates to novel compositions of matter. More particularly, the present invention relates to pyridyl substituted indenes and indoles. These compounds are potent thromboxane A.sub.2 inhibitors and as such represent useful pharmacological agents.
Since the discovery that human platelets convert the prostaglandin endoperoxide (PGH.sub.2) into a labile proaggregatory molecule known as thromboxane A.sub.2 (TXA.sub.2), researchers have sought compounds that could selectively inhibit the biological activity of TXA.sub.2. This end may be achieved in two different ways: the synthesis of TXA.sub.2 can be blocked by inhibiting the TXA.sub.2 synthetase, or a compound could be a receptor level antagonist of TXA.sub.2. As therapeutic agents, TXA.sub.2 synthetase inhibitors are more useful. See, e.g., R. Gorman, "Biological and Pharmacological Evaluation of Thomboxane Synthetase Inhibitors," Advances in Prostaglandin and Thromboxane Research, 6: 417 (1980), and references cited therein. Most important are compounds which selectively inhibit TXA.sub.2 synthetase. Id.
A number of TXA.sub.2 synthetase inhibitors are known. See for example the bi-heterocyclic 9,11-trideoxy-PGF-type compounds disclosed in U.S. Pat. No. 4,112,224; SQ 80,388 [1-(3-phenyl-2-propenyl)1H-imidazole] disclosed in D. Harris, et al., Advances in Prostaglandin and Thromboxane Research 6: 437 (1980); pyridine and its derivatives, disclosed in T. Miyamoto, et al., Advances in Prostaglandin and Thromoboxane Research, 6: 443 (1980), and British patent application 2,039,903A (abstracted in Derwent Farmdoc No. 50111C (1980)). See also H. Tai, et al., Advances in Prostaglandin and Thromboxane Research, 6: 447 (1980). Other compounds which have been disclosed as thromboxane synthetase inhibitors, include sodium p-benzyl-4(1-oxo-2-(4-chlorobenzyl)-3-phenylpropyl)phenyl phosphate, imidazoles, nordihydroguaiaretic acid, and 12L-hydroperoxy-5,8,10,14-eicosatetraenoic acid (HETE). As noted in the above named British patent specification, however, the inhibitory activity of these latter compounds on thromboxane synthetase is very weak making them unsatisfactory as practically effective medicines.